Filaggrin Expression and Processing Deficiencies Impair Corneocyte Surface Texture and Stiffness in Mice

Jacob P. Thyssen, Ivone Jakasa, Christoph Riethmüller, Michael P. Schön, Andrea Braun, Marek Haftek, Padraic G. Fallon, Jacek Wróblewski, Hieronim Jakubowski, Leopold Eckhart, Wim Declercq, Sjors Koppes, Kristiane A. Engebretsen, Charlotte Bonefeld, Alan D. Irvine, Sokhna Keita-Alassane, Michel Simon, Hiroshi Kawasaki, Akiharu Kubo, Masayuki AmagaiTakeshi Matsui, Sanja Kezic

研究成果: Article査読

14 被引用数 (Scopus)

抄録

Abundant corneocyte surface protrusions, observed in patients with atopic dermatitis with filaggrin loss-of-function mutations, are inversely associated with levels of natural moisturizing factors (NMFs) in the stratum corneum. To dissect the etiological role of NMFs and filaggrin deficiency in surface texture alterations, we examined mouse models with genetic deficiencies in the synthesis or degradation of filaggrin monomers for NMFs, cell stiffness (elastic modulus) and corneocyte surface protrusion density (dermal texture index). Five neonatal and adult mouse models carrying inactivating mutations of SASPase (Sasp−/−), filaggrin (Flgft/ft and Flg−/−), filaggrin-hornerin (FlgHrnr−/−), and bleomycin hydrolase (Blmh−/−) were investigated. Sasp−/− and Flg−/− were on the hairless mouse background. Atomic force microscopy was used to determine elastic modulus and dermal texture index. Corneocytes of each neonatal as well as hairless adult knockout mouse exhibited an increased number of protrusions and decreased elastic modulus. In these mice, NMFs were reduced except for Sasp−/−. Dermal texture index was inversely correlated with NMFs and elastic modulus. Our findings demonstrate that any filaggrin-NMF axis deficiency can affect corneocyte mechanical properties in mice and likely in humans. Differences in NMFs and corneocyte surface texture between neonatal and adult as well as hairless and hairy mice emphasize the need for carefully selecting the most appropriate animal models for studies.

本文言語English
ページ(範囲)615-623.e5
ジャーナルJournal of Investigative Dermatology
140
3
DOI
出版ステータスPublished - 2020 3月

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 皮膚病学
  • 細胞生物学

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